Change of Expression of Transcription Factor e2f-1 in Advancement of Gastric Cancer and Its Significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Hongbiao ¹ , WU Jugang ¹ , ZHANG Peng ¹ , NI Xiaochun ¹ , ZHANG Biao ¹ , SU Zhendong ¹ , LI Xiaoqiang ² , YU Jiwei ¹ , JIANG Bojian ¹

1.Department of General Surgery, No.3 People’s Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 201900, China;;
2.Department of Pathology, No.3 People’s Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 201900, China;

Corresponding author：

Keywords：

Stomach; Cancer; Neoplasma; Transcription factor e2f-1; Prognosis

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Objective To investigate the expression of transcription factor e2f-1 in the different development stages of gastric cancer, the relationships between clinicopathologic characteristics and e2f-1 expression status, as well as its influences on the prognosis. Methods The operative samples from primary lesion of 121 patients who underwent radical resection for gastric cancer were detected by SABC immunohistochemical staining. The relationships of e2f-1 expression with clinicopathologic characteristics and with the prognosis were observed by univariate, multivariate and relative analyses. Results The total positive expression rate of e2f-1 in all patients was 38.8% （47/121）. With the advancement of gastric cancer, the level of e2f-1 expression in TNMⅠ-Ⅳ stage was gradually decreased (r=－0.320， P lt;0.05)： Ⅰa stage with 62.5% （10/16）， Ⅰb with 47.1% （8/17）， Ⅱwith 55.0% （11/20）， Ⅲa with 40.0% （8/20）， Ⅲb with 27.3% （6/22）， Ⅳ with 15.4% （4/26）. The expression of e2f-1 was significantly negative correlated with tumor diameter, depth of infiltration, lymph node metastasis ratio, and N stage （P lt;0.05）. The multivariate analysis revealed that either histology type, or survival time was respectively an independent factor for e2f-1 expression （P lt;0.05）. Log-Rank test showed the relative factors to survival included N stage, tumor diameter, tumor position, lymph node metastasis ratio, depth of infiltration, and TNM stage （P lt;0.05）. Cox survival analysis found that both of later N stage and e2f-1 higher expression were independent prognostic factors （P lt;0.05）. The higher e2f-1 expression was related to a poor survival in TNM stageⅠand Ⅱ patients （r=－0.304, P lt;0.05）, the prognosis of patients with e2f-1 positive expression was worse than that of patients with negative expression （χ2=13.437， P lt;0.05）, and there was no statistic relationship between the expression of e2f-1 and prognosis in stage Ⅲ and Ⅳ patients （P gt;0.05）. Conclusions e2f-1, as a useful marker, seems to be an indication for the malignant behavior in relatively earlier gastric cancer, in which the e2f-1 positive expression shares a significantly poor survival. And the lower expression of e2f-1 has been identified in later advanced gastric cancer, the more malignances in advanced gastric cancer might associate with a lower expression of e2f-1.

Citation： WU Hongbiao,WU Jugang,ZHANG Peng,NI Xiaochun,ZHANG Biao,SU Zhendong,LI Xiaoqiang,YU Jiwei,JIANG Bojian. Change of Expression of Transcription Factor e2f-1 in Advancement of Gastric Cancer and Its Significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(6): 573-580. doi: Copy

1.	Mashta O. Stomach cancer incidence has halved over past 30 years in Britain [J]. BMJ, 2009; 339: b3281.
2.	Mousavi SM, Somi MH. Gastric cancer in Iran 1966-2006 [J]. Asian Pac J Cancer Prev, 2009; 10(3): 407-412.
3.	Li ZX, Kaminishi M. A comparison of gastric cancer between Japan and China [J]. Gastric Cancer, 2009; 12(1): 52-53.
4.	季加孚. 胃癌外科的发展趋势 [J]. 中国普外基础与临床杂志, 2006; 13(1): 1-3.
5.	朱正纲. 胃癌外科治疗相关问题的基本认识 [J]. 中国普外基础与临床杂志, 2008; 15 (1): 1-3.
6.	Cunningham D, Jost LM, Purkalne G, et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of gastric cancer [J]. Ann Oncol, 2005; 16 Suppl 1: i22-i23.
7.	Inoue M, Tsugane S. Epidemiology of gastric cancer in Japan [J]. Postgrad Med J, 2005; 81(957): 419-424.
8.	Seifried LA, Talluri S, Cecchini M, et al. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption [J]. J Virol, 2008; 82(9): 4511-4520.
9.	Findlay GM, Pawson T. How is SOS activated? Let us count the ways [J]. Nat Struct Mol Biol, 2008; 15(6): 538-540.
10.	Boykevisch S, Zhao C, Sondermann H, et al. Regulation of ras signaling dynamics by Sos-mediated positive feedback [J]. Curr Biol, 2006; 16(21): 2173-2179.
11.	Hinrichsen R, Hansen AH, Hauns S, et al. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy [J]. Cell Prolif, 2008; 41(5): 813-829.
12.	Ogino A, Yoshino A, Katayama Y, et al. The p15(INK4b)/p16(INK4a)/RB1 pathway is frequently deregulated in human pituitary adenomas [J]. J Neuropathol Exp Neurol, 2005; 64(5): 398-403.
13.	Valeyev NV, Heslop-Harrison P, Postlethwaite I, et al. Cr-osstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels [J]. Mol Biosyst, 2009; 5(1): 43-51.
14.	Seavilleklein G, Amer N, Evagelidis A, et al. PKC phosphorylation modulates PKA-dependent binding of the R domain to other domains of CFTR [J]. Am J Physiol Cell Physiol, 2008; 295(5): C1366-C1375.
15.	Sterin-Borda L, Bernabeo G, Ganzinelli S, et al. Role of nitric oxide/cyclic GMP and cyclic AMP in beta3 adrenoceptor-chronotropic response [J]. J Mol Cell Cardiol, 2006; 40(4): 580-588.
16.	Stites EC, Trampont PC, Ma Z, et al. Network analysis of oncogenic Ras activation in cancer [J]. Science, 2007; 318(5849): 463-467.
17.	Wu Z, Zheng S, Yu Q. The E2F family and the role of E2F1 in apoptosis [J]. Int J Biochem Cell Biol, 2009; 41(12): 2389-2397.
18.	Schayek H, Bentov I, Rotem I, et al. Transcription factor E2F1 is a potent transactivator of the insulin-like growth factor-Ⅰ receptor (IGF-ⅠR) gene [J]. Growth Horm IGF Res, 2010; 20(1): 68-72.
19.	Lee KH, Chen YL, Yeh SD, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation [J]. Oncogene, 2009; 28(38): 3360-3370.
20.	Huang CL, Liu D, Nakano J, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer [J]. Clin Cancer Res, 2007; 13(23): 6938-6946.
21.	Cassimere EK, Pyndiah S, Sakamuro D. The c-MYC-interacting proapoptotic tumor suppressor BIN1 is a transcriptional target for E2F1 in response to DNA damage [J]. Cell Death Differ, 2009; 16(12): 1641-1653.
22.	Jenal M, Trinh E, Britschgi C, et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1 [J]. Mol Cancer Res, 2009; 7(6): 916-922.
23.	Worku D, Jouhra F, Jiang GW, et al. Evidence of a tumour suppressive function of E2F1 gene in human breast cancer [J]. Anticancer Res, 2008; 28(4B): 2135-2139.
24.	Ozaki T, Okoshi R, Ono S, et al. Deregulated expression of E2F1 promotes proteolytic degradation of tumor suppressor p73 and inhibits its transcriptional activity [J]. Biochem Biophys Res Commun, 2009; 387(1): 143-148.
25.	Liontos M, Niforou K, Velimezi G, et al. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas [J]. Am J Pathol, 2009; 175(1): 376-391.
26.	Alonso MM, Alemany R, Fueyo J, et al. E2F1 in gliomas: a paradigm of oncogene addiction [J]. Cancer Lett, 2008; 263(2): 157-163.
27.	Yu JW, Wu JG, Zheng LH, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma [J]. J Exp Clin Cancer Res, 2009; 28: 55.
28.	Suzuki T, Yasui W, Yokozaki H, et al. Expression of the E2F family in human gastrointestinal carcinomas [J]. Int J Cancer, 1999; 81(4): 535-538.
29.	Jamshidi-Parsian A, Dong Y, Zheng X, et al. Gene expression profiling of E2F-1-induced apoptosis [J]. Gene, 2005; 344: 67-77.
30.	Xie Y, Wang C, Li L, et al. Overexpression of E2F-1 inhibits progression of gastric cancer in vitro [J]. Cell Biol Int, 2009; 33(6): 640-649.

1. Mashta O. Stomach cancer incidence has halved over past 30 years in Britain [J]. BMJ, 2009; 339: b3281.
2. Mousavi SM, Somi MH. Gastric cancer in Iran 1966-2006 [J]. Asian Pac J Cancer Prev, 2009; 10(3): 407-412.
3. Li ZX, Kaminishi M. A comparison of gastric cancer between Japan and China [J]. Gastric Cancer, 2009; 12(1): 52-53.
4. 季加孚. 胃癌外科的发展趋势 [J]. 中国普外基础与临床杂志, 2006; 13(1): 1-3.
5. 朱正纲. 胃癌外科治疗相关问题的基本认识 [J]. 中国普外基础与临床杂志, 2008; 15 (1): 1-3.
6. Cunningham D, Jost LM, Purkalne G, et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of gastric cancer [J]. Ann Oncol, 2005; 16 Suppl 1: i22-i23.
7. Inoue M, Tsugane S. Epidemiology of gastric cancer in Japan [J]. Postgrad Med J, 2005; 81(957): 419-424.
8. Seifried LA, Talluri S, Cecchini M, et al. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption [J]. J Virol, 2008; 82(9): 4511-4520.
9. Findlay GM, Pawson T. How is SOS activated? Let us count the ways [J]. Nat Struct Mol Biol, 2008; 15(6): 538-540.
10. Boykevisch S, Zhao C, Sondermann H, et al. Regulation of ras signaling dynamics by Sos-mediated positive feedback [J]. Curr Biol, 2006; 16(21): 2173-2179.
11. Hinrichsen R, Hansen AH, Hauns S, et al. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy [J]. Cell Prolif, 2008; 41(5): 813-829.
12. Ogino A, Yoshino A, Katayama Y, et al. The p15(INK4b)/p16(INK4a)/RB1 pathway is frequently deregulated in human pituitary adenomas [J]. J Neuropathol Exp Neurol, 2005; 64(5): 398-403.
13. Valeyev NV, Heslop-Harrison P, Postlethwaite I, et al. Cr-osstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels [J]. Mol Biosyst, 2009; 5(1): 43-51.
14. Seavilleklein G, Amer N, Evagelidis A, et al. PKC phosphorylation modulates PKA-dependent binding of the R domain to other domains of CFTR [J]. Am J Physiol Cell Physiol, 2008; 295(5): C1366-C1375.
15. Sterin-Borda L, Bernabeo G, Ganzinelli S, et al. Role of nitric oxide/cyclic GMP and cyclic AMP in beta3 adrenoceptor-chronotropic response [J]. J Mol Cell Cardiol, 2006; 40(4): 580-588.
16. Stites EC, Trampont PC, Ma Z, et al. Network analysis of oncogenic Ras activation in cancer [J]. Science, 2007; 318(5849): 463-467.
17. Wu Z, Zheng S, Yu Q. The E2F family and the role of E2F1 in apoptosis [J]. Int J Biochem Cell Biol, 2009; 41(12): 2389-2397.
18. Schayek H, Bentov I, Rotem I, et al. Transcription factor E2F1 is a potent transactivator of the insulin-like growth factor-Ⅰ receptor (IGF-ⅠR) gene [J]. Growth Horm IGF Res, 2010; 20(1): 68-72.
19. Lee KH, Chen YL, Yeh SD, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation [J]. Oncogene, 2009; 28(38): 3360-3370.
20. Huang CL, Liu D, Nakano J, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer [J]. Clin Cancer Res, 2007; 13(23): 6938-6946.
21. Cassimere EK, Pyndiah S, Sakamuro D. The c-MYC-interacting proapoptotic tumor suppressor BIN1 is a transcriptional target for E2F1 in response to DNA damage [J]. Cell Death Differ, 2009; 16(12): 1641-1653.
22. Jenal M, Trinh E, Britschgi C, et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1 [J]. Mol Cancer Res, 2009; 7(6): 916-922.
23. Worku D, Jouhra F, Jiang GW, et al. Evidence of a tumour suppressive function of E2F1 gene in human breast cancer [J]. Anticancer Res, 2008; 28(4B): 2135-2139.
24. Ozaki T, Okoshi R, Ono S, et al. Deregulated expression of E2F1 promotes proteolytic degradation of tumor suppressor p73 and inhibits its transcriptional activity [J]. Biochem Biophys Res Commun, 2009; 387(1): 143-148.
25. Liontos M, Niforou K, Velimezi G, et al. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas [J]. Am J Pathol, 2009; 175(1): 376-391.
26. Alonso MM, Alemany R, Fueyo J, et al. E2F1 in gliomas: a paradigm of oncogene addiction [J]. Cancer Lett, 2008; 263(2): 157-163.
27. Yu JW, Wu JG, Zheng LH, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma [J]. J Exp Clin Cancer Res, 2009; 28: 55.
28. Suzuki T, Yasui W, Yokozaki H, et al. Expression of the E2F family in human gastrointestinal carcinomas [J]. Int J Cancer, 1999; 81(4): 535-538.
29. Jamshidi-Parsian A, Dong Y, Zheng X, et al. Gene expression profiling of E2F-1-induced apoptosis [J]. Gene, 2005; 344: 67-77.
30. Xie Y, Wang C, Li L, et al. Overexpression of E2F-1 inhibits progression of gastric cancer in vitro [J]. Cell Biol Int, 2009; 33(6): 640-649.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Change of Expression of Transcription Factor e2f-1 in Advancement of Gastric Cancer and Its Significances

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